Tyrosyl-DNA phosphodiesterase 1

The protein encoded by this gene is involved in repairing stalled topoisomerase I-DNA complexes by catalyzing the hydrolysis of the phosphodiester bond between the tyrosine residue of topoisomerase I and the 3-prime phosphate of DNA. This protein may also remove glycolate from single-stranded DNA containing 3-prime phosphoglycolate, suggesting a role in repair of free-radical mediated DNA double-strand breaks. This gene is a member of the phospholipase D family and contains two PLD phosphodiesterase domains. Mutations in this gene are associated with the disease spinocerebellar ataxia with axonal neuropathy (SCAN1). While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same isoform. [provided by RefSeq, Jul 2008] (from
NCBI)

This review is dedicated to one of these proteins, tyrosyl-DNA phosphodiesterase 1 (Tdp1), for which we have recently shown that in addition to its main activity of specific cleavage of the tyrosyl-DNA bond formed via a covalent attachment of topoisomerase 1 (Top1) to DNA, Tdp1 is able to initiate the cleavage of the internal AP sites in DNA and their following repair.

study identifies TDP1 as a target for modification by the small ubiquitin-like modifier SUMO and provides evidence implicating SUMOylation in facilitating TDP1 cellular function during single-strand break repair

The importance of liberating DNA termini from trapped topoisomerase is illustrated by the progressive neurodegenerative disease observed in individuals containing a mutation in tyrosyl-DNA phosphodiesterase 1 (TDP1), an enzyme that cleaves 3'-phosphotyrosyl bonds.